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  1. 1. ASSESSMENT: TRANSCRANIAL DOPPLER ULTRASONOGRAPHY Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2004;62(9):1468
  2. 2. Copyright 2004 American Academy of Neurolo2 Authors Michael A. Sloan, MD, MS; Andrei V. Alexandrov, MD, RVT; Charles H. Tegeler, MD; Merrill P. Spencer, MD; Louis R. Caplan, MD; Edward Feldmann, MD; Lawrence R. Wechsler, MD; David W. Newell, MD; Camilo R. Gomez, MD; Viken L. Babikian, MD; David Lefkowitz, MD; Robert S. Goldman, MD; Carmel Armon, MD; Chung Y. Hsu, MD, PhD; and Douglas S. Goodin, MD
  3. 3. Copyright 2004 American Academy of Neurolo3 Objective of the guideline To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis.
  4. 4. Copyright 2004 American Academy of Neurolo4 Methods of evidence review • Panel reviewed summary statements and other articles, based upon selection of relevant publications cited in these new articles and additional MEDLINE search through June, 2003 using the AAN rating system, • Articles reviewed and cited contain a mixture of diagnostic, therapeutic or prognostic information used as the reference standard in individual studies. • Sensitivity and specificity reflect the ability of a diagnostic test to detect disease. Reviewed for TCD and TCCS.
  5. 5. Copyright 2004 American Academy of Neurolo5 Methods of evidence review • Sensitivity and specificity were operationally defined as excellent (>/= 90%), good (80-89%), fair (60-79%) and poor (<60%). • The clinical utility of a diagnostic test was operationally defined as the value of the test result to the clinician caring for the individual patient. • Panel summarized the clinical utility of TCD/TCCS and focus on the clinical indications for which conclusions can be drawn.
  6. 6. Copyright 2004 American Academy of Neurolo6 AAN’s Class of evidence for determining the yield of established diagnostic and screening tests Class I: Evidence provided by prospective study in broad spectrum of persons who may be at risk of outcome (target disease, work status). Study measures predictive ability using independent gold standard to define cases. Predictor is measured in evaluation masked to clinical presentation. Outcome is measured in evaluation masked to presence of predictor. Class II: Evidence provided by prospective study of narrow spectrum of persons who may be at risk for having the condition, retrospective study of broad spectrum of persons with condition compared to broad spectrum of controls. Study measures prognostic accuracy of risk factor using acceptable independent gold standard to define cases. Risk factor is measured in evaluation masked to the outcome.
  7. 7. Copyright 2004 American Academy of Neurolo7 AAN’s Class of evidence for determining the yield of established diagnostic and screening tests Class III: Evidence provided by retrospective study where persons with condition or controls are of narrow spectrum. Study measures predictive ability using independent gold standard to define cases. Risk factor measured in evaluation masked to outcome. Class IV: Any design where predictor is not applied in masked evaluation OR evidence by expert opinion, case series.
  8. 8. Copyright 2004 American Academy of Neurolo8 AAN’s Recommendation levels Level A: Established as useful/ predictive or not useful/ predictive for the given condition in the specified population. >/= 1 convincing Class I or >/=2 consistent, convincing Class II studies. Level B: Probably useful/ predictive or not useful/ predictive for the given condition in the specified populations. >/= 1 convincing Class II or >/=3 consistent Class III studies
  9. 9. Copyright 2004 American Academy of Neurolo9 AAN’s Recommendation levels Level C: Possibly useful/ predictive or not useful/ predictive for the given condition in the specified population. >/=2 convincing and consistent Class III studies Level U: Data inadequate or conflicting. Given current knowledge, test/predictor unproven.
  10. 10. Copyright 2004 American Academy of Neurolo10 Introduction • TCD is a non-invasive ultrasonic technique measuring local blood flow velocity and direction in the proximal portions of large intracranial arteries. • TCD’s principal use is in the evaluation and management of patients with cerebrovascular disease.
  11. 11. Copyright 2004 American Academy of Neurolo11 Introduction • Advantages of TCD: – non-invasive – can be performed at the bedside – easily repeated or used for continuous monitoring – is generally less expensive than other techniques – contrast agents are not used avoiding allergic reactions and decreasing risk to the patient
  12. 12. Copyright 2004 American Academy of Neurolo12 Introduction • Limitation of TCD: – examination of cerebral blood flow velocities in certain segments of large intracranial vessels – detects indirect effects (abnormal waveform characteristics) suggesting of proximal hemodynamic or distal obstructive lesions – more valuable in specific conditions
  13. 13. Conventional or Non-imaging TCD
  14. 14. Copyright 2004 American Academy of Neurolo14 Summary of findings Sickle Cell Disease INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Sickle Cell Disease 86 91 Conventional angiography Recommendation: TCD screening of children with SCD between the ages of 2 and 16 years is effective for assessing stroke risk (Type A, Class I evidence), although the optimal frequency of testing is unknown (Type U).
  15. 15. Copyright 2004 American Academy of Neurolo15 Summary of findings Right to Left Cardiac Shunts INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Right to Left Cardiac Shunts 70-100 >95 Transesophageal echocardiography Recommendation: Contrast TCD is comparable to contrast TEE for detecting right to left shunts due to PFO (Type A, Class II evidence). TEE is superior than contrast TCD since it provides direct anatomic information regarding the site and nature of the shunt or presence of an ASA. While the number of microbubbles reaching the brain can be quantified by TCD, the therapeutic impact of this additional information is unknown (Type U).
  16. 16. Copyright 2004 American Academy of Neurolo16 Summary of findings Intracranial Steno-Occlusive Disease INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Intracranial Steno-Occlusive Disease: Conventional angiography Anterior Circulation 70-90 90-95 Posterior Circulation Occlusion 50-80 80-96
  17. 17. Copyright 2004 American Academy of Neurolo17 Summary of findings Intracranial Steno-Occlusive Disease (Continued ) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD MCA 85-95 90-98 ICA, VA, BA 55-81 96 Recommendation: Data are insufficient to establish TCD criteria for greater than 50% stenosis or for progression of stenosis in intracranial arteries (Type U).
  18. 18. Copyright 2004 American Academy of Neurolo18 Summary of findings Acute cerebral infarction INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Acute cerebral infarction 85-95 90-98 Recommendation: TCD is probably useful for the evaluation of patients with suspected intracranial steno-occlusive disease, particularly in the ICA siphon and MCA (Type B, Class II evidence). The relative value of TCD compared with MRA or CTA remains to be determined (Type U). Data are insufficient to give a recommendation regarding replacing conventional angiography with TCD (Type U).
  19. 19. Copyright 2004 American Academy of Neurolo19 Summary of findings Extracranial ICA Stenosis INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Extracranial ICA Stenosis: Conventional angiography Single TCD variable 3-78 60-100 TCD Battery 49-95 42-100 TCD Battery & Carotid Duplex 89 100 Recommendation:TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion (Type C, Class II- III evidence).
  20. 20. Copyright 2004 American Academy of Neurolo20 Summary of findings Vasomotor Reactivity (VMR) Testing INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Vasomotor Reactivity (VMR) Testing >/= 70% extracranial ICA stenosis / occlusion Conventional angiography, clinical outcomes
  21. 21. Copyright 2004 American Academy of Neurolo21 Summary of findings Vasomotor Reactivity (VMR) Testing (continued) Recommendation: TCD vasomotor reactivity testing is considered probably useful for –the detection of impaired cerebral hemodynamics in patients with asymptomatic severe (>70%) stenosis of the extracranial ICA –patients with symptomatic or asymptomatic extracranial ICA occlusion and patients with cerebral small artery disease (Type B, Class II-III evidence). How the results from these techniques should be used to influence therapy and affect patient outcomes remains to be determined (Type U).
  22. 22. Copyright 2004 American Academy of Neurolo22 Summary of findings Detection of Cerebral Microemboli INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Cerebral Microembolization Experimental model, pathology, magnetic resonance imaging, neuropsychological tests Recommendation: TCD is probably useful to detect cerebral microembolic signals in a wide variety of cardiovascular/ cerebrovascular disorders/procedures (Type B, Class II-IV evidence). However, data at present do not support the use of TCD for diagnosis or for monitoring response to antithrombotic therapy in ischemic cerebrovascular disease in these settings(Type U).
  23. 23. Perioperative and Periprocedural Monitoring
  24. 24. Copyright 2004 American Academy of Neurolo24 Summary of findings Carotid Endarterectomy (CEA) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Carotid Endarterectomy (CEA): EEG, magnetic resonance imaging, clinical outcomes Recommendation: CEA monitoring with TCD can provide important feedback pertaining to hemodynamic and embolic events during and after surgery that may help the surgeon take appropriate measures at all stages of the operation to reduce the risk of perioperative stroke. TCD monitoring is probably useful during and after CEA in circumstances where monitoring is felt to be necessary (Type B, Class II-III evidence).
  25. 25. Copyright 2004 American Academy of Neurolo25 Summary of findings Coronary Artery Bypass Graft (CABG) Surgery INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Coronary Artery Bypass Graft (CABG) Surgery Recommendation: TCD is possibly effective in documenting changes in flow velocities and CO2 reactivity in patients who undergo CABG (Type C, Class III evidence). TCD is probably useful for the detection and monitoring of cerebral microemboli in patients undergoing CABG (Type B, Class II-III evidence). Data are presently insufficient regarding the clinical utility of this information (Type U).
  26. 26. Copyright 2004 American Academy of Neurolo26 Summary of findings Cerebral Thrombolysis INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Cerebral Thrombolysis Conventional angiography, magnetic resonance angiography, clinical outcome Complete Occlusion 50 100 Partial Occlusion 100 76 Recanalization 91 93
  27. 27. Copyright 2004 American Academy of Neurolo27 Summary of findings Cerebral Thrombolysis (continued) Recommendation: TCD is probably useful for monitoring thrombolysis of acute MCA occlusions (Type B, Class II-III evidence). Present data are insufficient to either define the optimal frequency of TCD monitoring for clot dissolution and enhanced recanalization or to influence therapy (Type U).
  28. 28. Monitoring in the Neurology/ Neurosurgery Intensive Care Unit
  29. 29. Copyright 2004 American Academy of Neurolo29 Summary of findings Subarachnoid Hemorrhage (SAH): INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Vasospasm after Spontaneous Subarachnoid Hemorrhage Conventional angiography Intracranial ICA 25-30 83-91 MCA 39-94 70-100 ACA 13-71 65-100 VA 44-100 82-88
  30. 30. Copyright 2004 American Academy of Neurolo30 Summary of findings Subarachnoid Hemorrhage (SAH) (continued) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD BA 77-100 42-79 PCA 48-60 78-87 Recommendations: TCD is useful for the detection and monitoring of angiographic VSP in the basal segments of the intracranial arteries, especially the MCA and BA, following sSAH (Type A, Class I-II evidence). More data are needed to show if TCD affects clinical outcomes in this setting (Type U).
  31. 31. Copyright 2004 American Academy of Neurolo31 Summary of findings Traumatic SAH (tSAH) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Vasospasm after Traumatic Subarachnoid Hemorrhage Conventional angiography Recommendation: TCD is probably useful for the detection of VSP and cerebral hemodynamic impairment following tSAH (Type B, Class I-III evidence). Data on sensitivity, specificity and predictive value of TCD for VSP after tSAH are needed. Data are insufficient regarding how use of TCD affects clinical outcomes after tSAH (Type U).
  32. 32. Copyright 2004 American Academy of Neurolo32 Summary of findings Increased Intracranial Pressure (ICP) and Cerebral Circulatory Arrest INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Cerebral Circulatory Arrest and Brain Death 91-100 97-100 Conventional angiography, EEG, clinical outcome Recommendation: TCD is a useful adjunct test for the evaluation of cerebral circulatory arrest associated with brain death (Type A, Class II evidence).
  33. 33. Transcranial Color-Coded Sonography (TCCS) or Imaging TCD
  34. 34. Copyright 2004 American Academy of Neurolo34 Transcranial Color-Coded Sonography (TCCS) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Transcranial Color-Coded Sonography (TCCS), with/without contrast enhancement Conventional angiography, pathology
  35. 35. Copyright 2004 American Academy of Neurolo35 Summary of findings Ischemic Cerebrovascular Disease INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD ACoA Collateral Flow 100 100 PCoA Collateral Flow 85 98
  36. 36. Copyright 2004 American Academy of Neurolo36 Summary of findings Ischemic Cerebrovascular Disease (Continued) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Intracranial Steno- Occlusive Lesions Any Up to 100 Up to 83
  37. 37. Copyright 2004 American Academy of Neurolo37 Summary of findings Ischemic Cerebrovascular Disease (Continued) INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD >/= 50% Stenosis MCA 100 100 ACA 100 100 VA 100 100 BA 100 100 PCA 100 100
  38. 38. Copyright 2004 American Academy of Neurolo38 Summary of findings Ischemic Cerebrovascular Disease (Continued) Recommendation: (CE)-TCCS is probably useful in the evaluation and monitoring of patients with ischemic cerebrovascular disease (Type B, Class II-IV evidence).
  39. 39. Copyright 2004 American Academy of Neurolo39 Summary of findings Hemorrhagic Cerebrovascular Disease INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Parenchymal Hypoechogenicity in MCA Distribution 69 83 Computed tomographic scan Recommendation: (CE-) TCCS is probably useful in the evaluation and monitoring of patients with aneurysmal SAH or intracranial ICA/MCA VSP following SAH (Type B, Class II-III evidence). Data are insufficient regarding the use of TCCS to replace CT for diagnosis of ICH (Type U).
  40. 40. Copyright 2004 American Academy of Neurolo40 Summary of findings Vasospasm after Spontaneous Subarachnoid Hemorrhage INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Vasospasm after Spontaneous Subarachnoid Hemorrhage 69 83 Conventional angiography Intracranial ICA 100 97 MCA 100 93 ACA 71 85
  41. 41. Copyright 2004 American Academy of Neurolo41 Summary of findings Intracerebral Hemorrhage INDICATION SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Intracerebral Hemorrhage 94 95 Computed tomographic scan Recommendation:There are insufficient data to support the routine clinical use of TCD/TCCS for other indications including: migraine, cerebral venous thrombosis, monitoring during cerebral angiography, evaluation of arteriovenous malformations, evaluation of cerebral autoregulation in other settings (Type U recommendation).
  42. 42. Copyright 2004 American Academy of Neurolo42 Summary of TCD recommendations Settings in which TCD is able to provide information and in which its clinical utility is established • Screening of children aged 2-16 years with sickle cell disease for assessing stroke risk (Type A, Class I), although the optimal frequency of testing is unknown (Type U). • Detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I-II). More data are needed to show if its use affects clinical outcomes (Type U).
  43. 43. Copyright 2004 American Academy of Neurolo43 Summary of TCD recommendations Settings in which TCD is able to provide information, but in which its clinical utility remains to be determined • Cerebral Thrombolysis: TCD is probably useful for monitoring thrombolysis of acute MCA occlusions (Type B, Class II-III). More data are needed to assess the frequency of monitoring for clot dissolution and enhanced recanalization and to influence therapy (Type U). • Cerebral Microembolism Detection: TCD monitoring is probably useful for the detection of cerebral microembolic signals in a variety of cardiovascular/ cerebrovascular disorders/procedures (Type B, Class II-IV). Data do not support the use of this TCD technique for diagnosis or monitoring response to antithrombotic therapy in ischemic cerebrovascular disease (Type U).
  44. 44. Copyright 2004 American Academy of Neurolo44 Summary of TCD recommendations Settings in which TCD is able to provide information, but in which its clinical utility remains to be determined • Carotid Endarterectomy: TCD monitoring is probably useful to detect hemodynamic and embolic events that may result in perioperative stroke during and after CEA in settings where monitoring is felt to be necessary (Type B, Class II-III). • Coronary Artery Bypass Graft (CABG) Surgery: TCD monitoring is probably useful (Type B, Class II-III) during CABG for detection of cerebral microemboli. TCD is possibly useful to document changes in flow velocities and CO2 reactivity during CABG surgery (Type C, Class III). Data are insufficient regarding the clinical impact of this information (Type U).
  45. 45. Copyright 2004 American Academy of Neurolo45 Summary of TCD recommendations Settings in which TCD is able to provide information, but in which its clinical utility remains to be determined • Vasomotor Reactivity Testing: TCD is probably useful (Type B, Class II-III) for the detection of impaired cerebral hemodynamics in patients with severe (>70%) asymptomatic extracranial ICA stenosis, symptomatic or asymptomatic extracranial ICA occlusion and cerebral small artery disease. Whether these techniques should be used to influence therapy and improve patient outcomes remains to be determined (Type U). • Vasospasm after traumatic subarachnoid hemorrhage: TCD is probably useful for the detection of VSP following traumatic SAH (Type B, Class III), but data are needed to show its accuracy and clinical impact in this setting (Type U).
  46. 46. Copyright 2004 American Academy of Neurolo46 Summary of TCD recommendations Settings in which TCD is able to provide information, but in which its clinical utility remains to be determined • Transcranial Color-Coded Sonography: TCCS is possibly useful (Type C, Class III) for the evaluation and monitoring of space-occupying ischemic MCA infarctions. More data are needed to show if it has value vs. CT and MRI scanning and if its use affects clinical outcomes (Type U).
  47. 47. Copyright 2004 American Academy of Neurolo47 Summary of TCD recommendations Settings in which TCD is able to provide information, but in which other diagnostic tests are typically preferable • Right-to-left cardiac shunts: While TCD is useful for detection of right-to-left cardiac and extracardiac shunts (Type A, Class II), TEE is superior, as it can provide direct information regarding the anatomic site and nature of the shunt. • Extracranial ICA Stenosis: TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion (Type C, Class II-III) but, in general, carotid duplex or MRA are the diagnostic tests of choice. • Contrast-Enhanced Transcranial Color-Coded Sonography: (CE)-TCCS may provide information in patients with ischemic cerebrovascular disease and aneurysmal SAH (Type B, Class II-IV). Its clinical utility vs. CT scanning, conventional angiography or non-imaging TCD, is unclear (Type U).
  48. 48. Copyright 2004 American Academy of Neurolo48 Recommendations for future research Ischemic Cerebrovascular Disease • Sickle Cell Disease: The optimal frequency for screening children between the ages of 2 and 16 years needs to be determined. Data are needed to assess the value of TCD in the evaluation of adults with sickle cell disease and its impact, if any, on selection of treatment and prognosis.
  49. 49. Copyright 2004 American Academy of Neurolo49 Recommendations for future research • Intracranial Steno-Occlusive Disease: More data are needed to define the ability of TCD to detect >/= 50% stenosis of major basal intracranial arteries vs. MRA and CTA. Once MRA and CTA are validated, the determination of the relative value of each technique for specific vascular lesions which may influence patient management. The ability of TCD to predict outcome in vertebrobasilar distribution stroke, if any, requires study. The value of TCD in the prediction of hemorrhagic transformation of ischemic infarction needs confirmation in well designed studies of patients who do and do not receive anticoagulation or thrombolysis.
  50. 50. Copyright 2004 American Academy of Neurolo50 Recommendations for future research • Extracranial ICA Stenosis: The clinical utility of TCD’s ability to detect impaired cerebral hemodynamics distal to high grade extracranial ICA stenosis or occlusion and assist with stroke risk assessment needs confirmation and evaluation in randomized clinical trials. In patients with symptomatic ICA occlusion, it would be useful to directly compare TCD/vasomotor reactivity testing with PET to see if TCD would be valuable to select and serially monitor patients for extracranial to intracranial bypass surgery. In patients with asymptomatic high grade ICA stenosis, it would be useful to learn if TCD assessment of vasomotor reactivity or microembolic signal detection can improve selection of patients for CEA or angioplasty.
  51. 51. Copyright 2004 American Academy of Neurolo51 Recommendations for future research Perioperative and Periprocedural Monitoring • Cerebral Microembolization: The ability of TCD to better distinguish between the various types of microembolic signals needs to be enhanced. Clinical utility in specific disease states should be defined. • Carotid Endarterectomy: The incremental value of TCD monitoring compared with other intraoperative monitoring procedures (EEG, evoked potentials, stump pressures, cerebral blood flow) needs further study.
  52. 52. Copyright 2004 American Academy of Neurolo52 Recommendations for future research Perioperative and Periprocedural Monitoring • Coronary Artery Bypass Graft (CABG) Surgery: More data are needed to show if TCD predicts the occurrence of stroke or neurocognitive impairment following CABG or be useful as a biomarker or surrogate endpoint for clinical trials of neuroprotective agents or new surgical techniques. • Cerebral Thrombolysis: The value of TCD in monitoring thrombolytic therapy (intravenous and intra-arterial) and other recanalizing techniques needs to be shown in clinical trials. Data from such studies might help in determining the need for further interventions and predicting the outcome of treated and non-treated patients. In addition, studies should be done to determine if thrombolysis can be enhanced with specific frequency(ies) of transcranial ultrasound.
  53. 53. Copyright 2004 American Academy of Neurolo53 Recommendations for future research Monitoring in the Neurology / Neurosurgery Intensive Care Unit • Spontaneous Subarachnoid Hemorrhage: More data are needed on the sensitivity and specificity of TCD in the detection of angiographic VSP in different age groups, since diagnostic criteria (like normative data) may vary with age. It remains to be shown how use of TCD affects clinical outcomes. The ability of specific TCD measurements to predict long term outcome from SAH requires study. • Traumatic Subarachnoid Hemorrhage: Data on the sensitivity and specificity of TCD for detection of angiographic VSP in this setting are needed. More data are needed to show the clinical utility and predictive power of TCD in this setting.
  54. 54. Copyright 2004 American Academy of Neurolo54 Recommendations for future research Monitoring in the Neurology/Neurosurgery Intensive Care Unit • Contrast-Enhanced Transcranial Color-Coded Sonography: The incremental value of (CE)-TCCS in diverse settings of ischemic and hemorrhagic cerebrovascular disease, in comparison to TCD, CT, CTA, MRI, MRA and conventional angiography, needs to be confirmed. Whether (CE)-TCCS can assist stroke and NeuroICU clinicians in the monitoring of reperfusion techniques or selection of patients with severe MCA territory infarction for clinical trials of aggressive, putative beneficial or life-saving therapies remains to be determined.
  55. 55. Copyright 2004 American Academy of Neurolo55 To view the entire guideline and additional AAN guidelines visit: www.aan.com/professionals/practice/index.cfm Neurology 2004;62(9):1468

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